Animal model or human cells: efficacy evidence for approved vaccines

“Live virus challenge studies were performed in mice, hamsters, cynomolgus macaques, and rhesus macaques.”

“The 2 lead antigens were tested for protective effect against SARS-CoV-2 challenge, at 10 μg level, with or without 5 ug Matrix-M1 adjuvant, in a prime-boost regime in mice sensitised for SARS-CoV-2 by intranasal instillation of adenovirus vector expressing human ACE2.”

“The Applicant has submitted three primary PD studies to characterise the immunogenicity of the PreF3-AS01E vaccine in mice and two immuno-characterization studies.”

“The Applicant has thoroughly explained that the non-clinical studies are only intended to show immunogenicity and not to evaluate vaccine efficacy, because a good animal model that can mimic the intended human non-naïve elderly target population and the sensitivity to RSV-related disease upon infection is not present.”

“Primary pharmacodynamic studies in mice and monkeys show that the activation of the innate immunity by AS04 is paralleled by the induction of a strong and persistent specific immune response by the Cervarix vaccine.”

“Given the species specificity of HPV precluding the evaluation of any human HPV-16/18 vaccine in protection animal models, primary pharmacodynamic studies aimed at the preclinical evaluation of the immunogenicity of the HPV-16/18 L1 VLP AS04 vaccine were carried out in mice and Rhesus monkeys.”

“A better immunogenicity was obtained in mice when HBsAg was formulated with AS04C than with alum, as in a commercially available HepB vaccine.”

“The results from these studies show that RIV3 and rH3 are immunogenic and can induce serum HAI and nAb antibodies against the influenza strains present in the vaccine.”

“No specific non-clinical pharmacology studies including immunogenicity and challenge-protection studies in animal models have been performed with RIV4. There is large amount of pharmacodynamics data available in humans with both RIV3 and RIV4, both licensed in the US and manufactured using the same manufacturing process as that intended for EU.”

“In each of the 3 non-human primate species tested, the intramuscular administration of Gardasil, or it’s monovalent components, was found to elicit immune responses resulting in production of antibodies against the HPV VLP types present in the vaccine.”

“There is no animal model for human papillomavirus infection, however there are other species-specific papillomaviruses that have been studied in animal models.”

“The vaccine elicited a robust immune response in all the animals resulting in the production of antibodies against each of the nine HPV types (6, 11, 16, 18, 31, 33, 45, 52 and 58) present in the vaccine.”

“There is no animal model for human papilloma virus infection. Therefore, the vaccine could not be tested for protection in animals.”

“In-vivo potency testing in C3H mice showed the thiomersal-free vaccine to be highly potent and comparable to that of the thiomersal-containing formulation.”

“The immunogenicity of HBsAg adjuvanted with 1018 ISS has been evaluated in mice, rat and baboons.”

“The immunogenicity studies also demonstrated that the anti-HBV antibody response and more importantly the frequency of animals responding with antibody levels ≥10 mIU/ml (the defined threshold for seroprotection in humans) is depending on the 1018 ISS dose.”

“The vaccine schedule was 3 intramuscular (i.m.) injections on days 0, 14 and 28, except GSK041 study in monkeys and two mouse studies (LIMS 20110165, LIMS 20130320) designed with immunobridging objectives.”

“The pharmacology studies clearly establish the immunogenicity of PreHevbri in immunized mice and rats.”

“The suitability of rodent species for these studies was supported by their responsiveness to HBsAg.”

“Primary pharmacodynamics studied in mice to evaluate cellular and humoral anti-gE antigen immune responses and to select the optimal formulations”

“There is no appropriate animal model to study Varicella Zoster Virus (VZV) pathogenesis, latency or reactivation. Hence, no non-clinical data on protection against Herpes Zoster by vaccine candidates (challenge studies) were generated.”